A Phase II Trial of Humanized Anti‐Vascular Endothelial Growth Factor Antibody for the Treatment of Androgen‐Independent Prostate Cancer

Abstract

Objective: Vascular endothelial growth factor (VEGF) is a glycoprotein that is important in promoting tumor angiogenesis. Recombinant humanized anti (rhuMAb)-VEGF is a humanized murine monoclonal antibody that neutralizes VEGF activity and has shown promise in animal tumor models. Methods: To evaluate the efficacy and safety of single-agent rhuMAb VEGF in metastatic androgen-independent prostate cancer (AIPC), we treated 15 patients with 10 mg/kg rhuMAb VEGF every 14 days for six infusions (one cycle), followed by additional treatment for selected patients who had a response or were stable. Results: After one cycle, none of the 15 patients who were evaluable for tumor response had an objective complete or partial response. Three possible mixed responses were observed. No patient achieved a >50% decrease in serum prostate specific antigen (PSA) level after one cycle. Four patients (27%) had a PSA decline of <50%, three patients (20%) had a PSA level increase of <50%, and eight patients (53%) had a PSA increase of >50%. The median time to objective progression was 118 days, and the median time to PSA progression was 57 days. Toxicity was generally mild, with asthenia present in 6 (40%) of 15 patients. Severe hyponatremia developed in two patients, although the association with rhuMAb VEGF was unclear. Conclusions: We concluded that single-agent rhuMAb VEGF in this dose and with this schedule did not produce significant objective responses in patients with AIPC. Further development of this agent in patients with prostate cancer should focus on earlier stage disease or should evaluate it in combination with other therapies.

Open-label, clinical phase I studies of tasquinimod in patients with castration-resistant prostate cancer

“…In general, the PSA response of the anti-angiogenic agents as stand-alone therapies in metastatic androgen-independent prostate cancer is modest (Figg et al, 2001;Reese et al, 2001;Steinbild et al, 2007;Dahut et al, 2008).…”

VEGF Inhibitors and Prostate Cancer Therapy

“…The dose of bevacizumab was 10 mg/kg intravenously every 2 weeks for 6 infusions that made up one cycle, followed by additional treatments for those who achieved a response or had stable disease [32]. No prostate specific antigen (PSA) decline of > 50% was noted in the 14 patients who were evaluable for response although 4 patients had PSA declines of < 50%.…”

Preparation and testing of bevacizumab radioimmunoconjugates with Bismuth-213 and Bismuth-205 / Bismuth-206

“…26 Various possibilities of combination approaches to bevacizumab for androgen-independent prostate cancer have also been proposed. 3 We have successfully prepared and tested labeled monoclonal antibodies and proteins in vitro and have demonstrated their efficacy for targeted alpha therapy (TAT) in vivo with various cancer models. [11][12][13][14][15][16][17][18][19][20][21] One of the labeled TAT products (antimelanoma monoclonal antibody 9.2.27 labeled with alpha emitting radionuclide Bismuth-213) has been successfully tested in our ongoing Phase I melanoma trials.…”

“…This includes its use as a single agent in hormone refractory metastatic prostate cancer, relapsed metastatic breast cancer and in renal cell cancer that had progressed following therapy with interleukin-2 (IL-2). [3][4][5] It has also been combined with standard first line chemotherapy in metastatic colorectal cancer and stage IIIb/IV non-small-cell lung cancer (NSCLC). 6,7 In a recently presented update on the bevacizumab clinical trial for advanced colorectal cancer, the data from 4,000 patients showed that bevacizumab enables patients with advanced colorectal cancer (CRC) to live longer without progression of their disease and it is well tolerated.…”